Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain.
Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain.
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DOI：
10.1038/cddis.2011.125
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发表时间：
2011-12-08
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
除了在下丘脑中控制体重的作用外，瘦素还参与神经元功能、发育和存活的调节。最近的研究结果强调了瘦素对缺血性脑损伤的神经保护作用;然而，迄今为止，很少有人知道信号转导和转录激活因子（STAT）-3，瘦素受体转导途径的主要介质在大脑中的作用，在激素的有益作用。我们的数据表明，全身性急性管理瘦素产生神经保护大鼠永久性大脑中动脉闭塞（MCAo），显示了一个显着减少脑梗死体积和神经功能缺损诱导缺血后7天。通过将亚细胞分级分离方法与荧光标记相结合，我们观察到神经保护与缺血皮质中STAT 3磷酸化的细胞类型特异性调节相关。在缺血半暗带的星形胶质细胞中，瘦素诱导的核磷酸化STAT 3的早期增强可能有助于这些细胞对组织损伤的演变的有益作用。此外，升高的磷酸化STAT 3的瘦素诱导的神经元后24小时MCAo与组织抑制剂的基质金属蛋白酶-1在皮层的表达增加，这表明其可能参与的神经保护所产生的脂肪因子。
In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine.
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影响因子：
2.8
作者：
Sierra-Johnson, Justo;Romero-Corral, Abel;Somers, Virend Kristen
通讯作者：
Somers, Virend Kristen
影响因子：
11.1
作者：
Söderberg, S;Stegmayr, B;Olsson, T
通讯作者：
Olsson, T
影响因子：
4.8
作者：
García-Cáceres C;Fuente-Martín E;Burgos-Ramos E;Granado M;Frago LM;Barrios V;Horvath T;Argente J;Chowen JA
通讯作者：
Chowen JA
DOI：
10.1006/bbrc.2000.2937
发表时间：
2000-06-24
影响因子：
3.1
作者：
Hosoi, T;Okuma, Y;Nomura, Y
通讯作者：
Nomura, Y
影响因子：
120.7
作者：
Heymsfield, SB;Greenberg, AS;McCamish, M
通讯作者：
McCamish, M